The evidence on vaccine efficacy waning is somewhat confusing to me!
On the one hand: Some of the initial data on waning from Israel (using Pfizer) was hopelessly confounded with age, leading to a huge Simpson’s paradox effect. Once you (a) figure out the Bayes error (they calculated Pr(vax | hospitalization) when they really wanted Pr(hospitalization | vax)), (b) properly stratify by age, and (c) calculate confidence limits on vaccine efficacy, the effect goes away.
On the gripping hand: Both of those show the onset of “waning” coincident with the onset of the Delta variant, i.e., last summer. So was it really waning, or was it Delta? I can’t tell.
They show a waning effect with respect to initial infection, but continued robust protection against hospitalization (still 85-90%). That could be normal:
Antibodies do decrease with time. You’re not carrying huge blood levels of antibodies for every virus you’ve ever encountered thus far in your life.
But T-cells and memory B-cells are still there. When an antigen from a previous infection is presented to the relevant memory B-cells, they trigger production of antibodies which then stop the infection. That way you can be technically infected for a couple days while that happens, but be asymptomatic or mildly symptomatic, and quickly clear the infection.
So it might be that we’re just seeing antibodies fade, but which rapidly come back upon re-challenge with the virus.
On the (unnamed) fourth hand: I looked at a recent study by Townsend et al. at the Yale School of Public Health that analyzed 6 coronaviruses known to infect humans and related to SARS-CoV2, predicting that there’s a 50% chance of reinfection at 18 months. So maybe periodic boosters will be required because of waning immunity?
So… “I notice that I am confused.” But since all this is happening frighteningly quickly and we’re just learning how it all works, confusion is the normal state of affairs at the leading edge of science. Thus my confusion might be normal.
Or maybe I’m just plain old confused and need somebody to straighten me out. That’s also regrettably normal, at least for me.
Until then, it seems that 2 things are worth remembering:
Boosters do seem to work in terms of boosting ab levels, and don’t seem to cause any worse side effects than the first doses.
If there is waning, boosters are an effective strategy; if there is no waning, then because of the non-terrible side-effects, boosters are a safe strategy, i.e., unlikely to do much harm.
So I got a booster, and my spouse gets one in a few days when eligible.
The evidence on vaccine efficacy waning is somewhat confusing to me!
On the one hand: Some of the initial data on waning from Israel (using Pfizer) was hopelessly confounded with age, leading to a huge Simpson’s paradox effect. Once you (a) figure out the Bayes error (they calculated Pr(vax | hospitalization) when they really wanted Pr(hospitalization | vax)), (b) properly stratify by age, and (c) calculate confidence limits on vaccine efficacy, the effect goes away.
On the other hand: Later Israeli data presented at the Moderna booster hearing cleaned that up and showed there was a waning effect. Moderna did something similar with their vaccine, comparing the people in the treatment arm of their clinical trial vs those in the control arm who got the vaccine 6 months later when it read out, showing a waning effect between those 2 carefully matched groups with known distributions of age, race, gender, etc.
On the gripping hand: Both of those show the onset of “waning” coincident with the onset of the Delta variant, i.e., last summer. So was it really waning, or was it Delta? I can’t tell.
They show a waning effect with respect to initial infection, but continued robust protection against hospitalization (still 85-90%). That could be normal:
Antibodies do decrease with time. You’re not carrying huge blood levels of antibodies for every virus you’ve ever encountered thus far in your life.
But T-cells and memory B-cells are still there. When an antigen from a previous infection is presented to the relevant memory B-cells, they trigger production of antibodies which then stop the infection. That way you can be technically infected for a couple days while that happens, but be asymptomatic or mildly symptomatic, and quickly clear the infection.
So it might be that we’re just seeing antibodies fade, but which rapidly come back upon re-challenge with the virus.
On the (unnamed) fourth hand: I looked at a recent study by Townsend et al. at the Yale School of Public Health that analyzed 6 coronaviruses known to infect humans and related to SARS-CoV2, predicting that there’s a 50% chance of reinfection at 18 months. So maybe periodic boosters will be required because of waning immunity?
So… “I notice that I am confused.” But since all this is happening frighteningly quickly and we’re just learning how it all works, confusion is the normal state of affairs at the leading edge of science. Thus my confusion might be normal.
Or maybe I’m just plain old confused and need somebody to straighten me out. That’s also regrettably normal, at least for me.
Until then, it seems that 2 things are worth remembering:
Boosters do seem to work in terms of boosting ab levels, and don’t seem to cause any worse side effects than the first doses.
If there is waning, boosters are an effective strategy; if there is no waning, then because of the non-terrible side-effects, boosters are a safe strategy, i.e., unlikely to do much harm.
So I got a booster, and my spouse gets one in a few days when eligible.